Nishimoto, Yoshinori

写真a

Affiliation

School of Medicine, Department of Internal Medicine (Neurology) (Shinanomachi)

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)

Career 【 Display / hide

  • 2022.04
    -
    Present

    慶應義塾大学 医学部, 神経内科, 専任講師

  • 2020.04
    -
    2022.03

    慶應義塾大学医学部, 神経内科, 助教

  • 2018.04
    -
    2020.03

    慶應義塾大学医学部, 百寿総合研究センター, 特任助教

  • 2016.10
    -
    2018.03

    東京都済生会中央病院, 神経内科, 医員

  • 2016.08
    -
    2018.03

    慶應義塾大学 医学部, 生理学教室, 助教

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Academic Background 【 Display / hide

  • 2003.04

    Keio University Graduate School of Medicine, Internal Medicine, Neurology

    Graduate School, Graduated, Doctoral course

  • 1997.04

    Keio University, Shool of Medicine

    University, Graduated

Academic Degrees 【 Display / hide

  • MD, Keio University, Coursework, 2003.03

  • PhD, Keio University, Coursework, 2008.10

    Determination of editors at the novel A-to-I editing positions.

Licenses and Qualifications 【 Display / hide

  • 日本国 医師免許

  • 日本内科学会認定 総合内科専門医

  • 日本内科学会認定 認定内科医

  • 日本内科学会認定 指導医

  • 日本神経学会認定 神経内科専門医

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Research Areas 【 Display / hide

  • Life Science / Neurology

Research Keywords 【 Display / hide

  • 筋萎縮性側索硬化症 (ALS)

  • 神経変性疾患

  • 神経分子生物学

  • 神経再生医学

  • RNA/ノンコーディングRNA

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Research Themes 【 Display / hide

  • Establishment of full-care system for the patients with amyotrophic lateral sclerosis (ALS), 

    2003.04
    -
    Present

  • 筋萎縮性側索硬化症(ALS)の核酸医薬による分子標的療法の開発, 

    2010.07
    -
    Present

  • 次世代シークエンス技術を活用した認知症の遺伝的リスク算出法の確立, 

    2018.04
    -
    Present

  • 認知症のオンライン診療データを活用した自動病態評価技術の開発, 

    2020.07
    -
    Present

 

Books 【 Display / hide

  • 脳神経内科ゴールデンハンドブック (ALSほか運動ニューロン疾患 分担執筆)

    西本 祥仁, 南江堂, 2020.06

    Scope: 運動ニューロン疾患及び類縁疾患

  • Chapter I 高齢者社会の現状とフレイル・ロコモ・サルコペニアの意義 3.百寿とはどのような方か?

    西本祥仁, 新井康通, クリニコ出版, 2019.11

  • Drosophila Oogenesis: Methods and Protocols

    Shibata S, Murota Y, Nishimoto Y, Yoshimura M, Nagai T, Okano H, Siomi MC., 2015

    Scope: Immuno-Electron Microscopy and Electron Microscopic In Situ Hybridization for Visualizing piRNA Biogenesis Bodies in Drosophila Ovaries.

Papers 【 Display / hide

  • Association between multimorbidity, self-rated health and life satisfaction among independent, community-dwelling very old persons in Japan: longitudinal cohort analysis from the Kawasaki Ageing and Well-being Project

    Ando T., Nishimoto Y., Hirata T., Abe Y., Takayama M., Maeno T., Fujishima S., Takebayashi T., Arai Y.

    BMJ Open (BMJ Open)  12 ( 2 )  2022

     View Summary

    Objective This study aimed to identify associations between multimorbidity and subjective health outcomes among the very old persons, after adjusting for coexisting conditions such as frailty and depression. Study setting and participants This was an observational cross-sectional study involving 1012 independent, community-dwelling very old persons (507 men, 505 women; aged 85-89 years) in Kawasaki city, Japan. Outcome measures The primary outcome was the cross-sectional associations between multimorbidity and poor self-rated health (SRH) and life satisfaction using binary logistic regression. The secondary outcome was the association of subjective health with each chronic condition. Results The prevalence of multimorbidity (≥2 conditions) was 94.7%, and the average number of chronic conditions was 4.47±1.9. Multimorbidity was significantly associated with poor SRH in the adjusted model only when six or more chronic conditions were present (OR 4.80; 95% CI 1.34 to 17.11; p=0.016). Cerebrovascular disease, heart disease, respiratory disease, connective tissue disease and arthritis showed significant associations with poor SRH after multivariate adjustment. Sex-specific analysis replicated associations between multimorbidity with six or more conditions and SRH in both men and women, while the diseases with the greatest impact on SRH differed between men and women. Most conditions were not associated with low satisfaction with life scale, with the exception of arthritis (OR 1.92, 95% CI 1.32 to 2.78, p=0.001). Conclusions Multimorbidity is prevalent in the independent, community-dwelling very old persons and is associated with poor SRH when six or more conditions are present; conditions causing mobility limitations, such as cerebrovascular disease, connective tissue disease and arthritis, have a negative impact on SRH. Trial registration number UMIN000026053.

  • ALDH2 p.E504K Variation and Sex Are Major Factors Associated with Current and Quitting Alcohol Drinking in Japanese Oldest Old

    Takashi Sasaki, Yoshinori Nishimoto, Takumi Hirata, Yukiko Abe, Toru Takebayashi, Yasumichi Arai

    Genes (Genes)  12 ( 6 )  2021

    Accepted

     View Summary

    This study identified the factors associated with current and quitting alcohol drinking in the Oldest Old to better understand the associated factors and mechanisms underlying drinking behaviors in this age group. Results of a questionnaire for drinking behavior in 1015 Japanese Oldest Old citizens aged 85 to 89 years revealed that 56.0% of men and 24.0% of women were current drinkers. A genome-wide association study revealed that the rs671 G > A variation, which corresponds to the aldehyde dehydrogenase 2 (ALDH2) p.E504K missense variant, was significantly associated with current drinking (odds ratio: 3.8, p = 3.33 × 10−31 ). Variable selection with 41 factors and multivariate regression logistic analysis for current drinking indicated that the rs671 genotype and sex were the most significant factors in the Oldest Old. Further analysis revealed that the rs671 genotype, alcohol-associated biomarkers, a history of heart or kidney disease, and frailty score are factors associated with quitting drinking in the Oldest Old men, whereas smoking history, walking time, and depression score were factors associated with quitting drinking in the Oldest Old women. These results indicate that the ALDH2 p.E504K variation is a major factor associated with current and quitting drinking in the Japanese Oldest Old.

  • NEAT1 lncRNA and amyotrophic lateral sclerosis

    Yoshinori Nishimoto, Shinichi Nakagawa, Hideyuki Okano

    Neurochemistry International (Neurochemistry International)  150 2021

    Research paper (scientific journal), Accepted,  ISSN  01970186

     View Summary

    Amyotrophic lateral sclerosis (ALS) is a representative neurological disease that is known to devastate entire motor neurons within a period of just a few years. Discoveries of the specific pathologies of relevant RNA-binding proteins, including TAR DNA-binding protein-43 (TDP-43) and fused in sarcoma/translocated in liposarcoma (FUS/TLS), and the causative genes of both familial and sporadic ALS have provided crucial information that could lead to a cure. In recent ALS research the GGGGCC-repeat expansion in the C9orf72 gene was identified as one of the most important pathological findings, suggesting the significance of both nuclear dysfunction due to dipeptide repeat proteins (DPRs) and RNA toxicity (such as pathological alterations of non-coding RNAs). In research on model animals carrying ALS-related molecules, the determination of whether a factor is protective or toxic has been controversial. Herein, we review the findings regarding NEAT1 RNA and C9orf72 GGGGCC repeats associated with ALS, from the viewpoint of conversion from the protective stage in the nucleus in early-phase ALS to late-phase induction of cell death. This review will provide insights for the development of RNA effectors as novel ALS treatments.

  • HTRA1-Related Cerebral Small Vessel Disease: a Review of the Literature

    Masahiro Uemura, Hiroaki Nozaki, Taisuke Kato, Akihide Koyama, Naoko Sakai, Shouichirou Ando, Masato Kanazawa, Nozomi Hishikawa, Yoshinori Nishimoto, Kiran Polavarapu, Atchayaram Nalini, Akira Hanazono, Daisuke Kuzume, Akihiro Shindo, Mohammad El-Ghanem, Arata Abe, Aki Sato, Mari Yoshida, Takeshi Ikeuchi, Ikuko Mizuta, Toshiki Mizuno, Osamu Onodera

    Frontiers in Neurology (Frontiers in Neurology)  11 2020

    Research paper (scientific journal), Accepted

     View Summary

    Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is clinically characterized by early-onset dementia, stroke, spondylosis deformans, and alopecia. In CARASIL cases, brain magnetic resonance imaging reveals severe white matter hyperintensities (WMHs), lacunar infarctions, and microbleeds. CARASIL is caused by a homozygous mutation in high-temperature requirement A serine peptidase 1 (HTRA1). Recently, it was reported that several heterozygous mutations in HTRA1 also cause cerebral small vessel disease (CSVD). Although patients with heterozygous HTRA1-related CSVD (symptomatic carriers) are reported to have a milder form of CARASIL, little is known about the clinical and genetic differences between the two diseases. Given this gap in the literature, we collected clinical information on HTRA1-related CSVD from a review of the literature to help clarify the differences between symptomatic carriers and CARASIL and the features of both diseases. Forty-six symptomatic carriers and 28 patients with CARASIL were investigated. Twenty-eight mutations in symptomatic carriers and 22 mutations in CARASIL were identified. Missense mutations in symptomatic carriers are more frequently identified in the linker or loop 3 (L3)/loop D (LD) domains, which are critical sites in activating protease activity. The ages at onset of neurological symptoms/signs were significantly higher in symptomatic carriers than in CARASIL, and the frequency of characteristic extraneurological findings and confluent WMHs were significantly higher in CARASIL than in symptomatic carriers. As previously reported, heterozygous HTRA1-related CSVD has a milder clinical presentation of CARASIL. It seems that haploinsufficiency can cause CSVD among symptomatic carriers according to the several patients with heterozygous nonsense/frameshift mutations. However, the differing locations of mutations found in the two diseases indicate that distinct molecular mechanisms influence the development of CSVD in patients with HTRA1-related CSVD. These findings further support continued careful examination of the pathogenicity of mutations located outside the linker or LD/L3 domain in symptomatic carriers.

  • Sex-specific effects of apolipo proteinε 4 alleleon mortality in very old and centenarian Japanese Men

    Sasaki T., Nishimoto Y., Abe Y., Takayama M., Hirose N., Okano H., Arai Y.

    Journals of Gerontology - Series A Biological Sciences and Medical Sciences (Journals of Gerontology - Series A Biological Sciences and Medical Sciences)  75 ( 10 ) 1874 - 1879 2020

    Accepted,  ISSN  10795006

     View Summary

    The apolipoprotein E4 (APOE ε4) allele has attracted attention as an age-related genetic factor, both in neurology and gerontology. To understand the effects of the APOE ε4 allele on mortality in elderly individuals, we combined Japanese prospective cohort studies comprising 535 very old individuals (85–99 years of age) and 930 centenarians (over 100 years of age) and analyzed the association between mortality rates and candidate factors, including the APOE ε4 allele. APOE genotyping revealed an inverse correlation between the APOE ε4 allele carrier rate and age. Additionally, APOE ε4 allele carrier rate in centenarian men was significantly lower than that in centenarian women. The association analysis between APOE ε4 allele carriers and all-cause mortality indicated that APOE ε4 carriers showed significantly higher mortality rates than the APOE ε4 noncarriers among men in the very old group. Further analysis using Cox proportional hazard models indicated that cause-specific mortalities, including pneumonia and severe dementia, were associated with APOE ε4 carriers. These findings indicate that the APOE ε4 allele shows phenotypic male-specific adverse effects in the very old, which would explain the high mortality rate observed in this group, resulting in a low APOE ε4 allele carrier rate in centenarian men.

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Papers, etc., Registered in KOARA 【 Display / hide

Research Projects of Competitive Funds, etc. 【 Display / hide

  • 文部科学省 科学研究費補助金 基盤研究(C) 「ALSゲノム編集マウスを用いたGC/UGリッチRNA配列での病態考察と治療法開発」

    2021.04
    -
    2025.03

    Research grant, Principal investigator

  • KGRI (Keio University Global Research Institute)スタートアップ研究補助 (KGRI startup award) 「オンライン診療を用いた認知症診療の有効性、安全性評価」

    2020.07
    -
    2022.03

    Research grant, Principal investigator

  • 日本ワックスマン財団 留学研究助成

    2013

    Research grant, No Setting

  • 文部科学省 科学研究費 補助金 (若手B) 「筋萎縮性側索硬化症におけるLIN28の細胞生存寄与に関する研究」

    2011.04
    -
    2013.03

    Research grant, Principal investigator

  • 慶應義塾大学医学部 研究補助金

    2011

    No Setting

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Works 【 Display / hide

  • 朝日学生新聞連載コラム「からだの教室 -知識の玉手箱-」

    西本 祥仁

    朝日学生新聞 毎週金曜日 全26回, 

    2014.04
    -
    2014.09

    Other

Awards 【 Display / hide

  • Neurogenetics Editor’s Pick 2021 (Frontiers in Neurology)

    2021.08

    Type of Award: Honored in official journal of a scientific society, scientific journal

  • KGRI (Keio University Global Research Institute) Startup Award

    2020.06, Keio University Global Research Institute, 「オンライン診療を用いた認知症診療の有効性、安全性評価」

    Type of Award: Keio commendation etc.

  • Selected key poster (Harvard Stem Cell Institute Retreat)

    2016.05, 11th Annual Harvard Stem Cell Institute Malkin Retreat 2016, 「Altered tRNA metabolism links RNA Exosome deficiency with motor neuron disease」

  • Physician's Recognition Award

    2015.08, American Medical Association, 「Pediatric Advanced Care Team Rounds」

  • 日本学術振興会 海外特別研究員

    2014.08

    Type of Award: Other

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Courses Taught 【 Display / hide

  • LECTURE SERIES, INTERNAL MEDICINE (NEUROLOGY)

    2022

  • LECTURE SERIES, INTERNAL MEDICINE (NEUROLOGY)

    2021